biostudies-literatureValls GNICHD NIH HHSNIDDK NIH HHSPHS HHSNIGMS NIH HHS5288-301https://www.ebi.ac.uk/biostudies/studies/S-EPMC3561852biostudies-literatureUnknown125(Pt 22)A role for Rac1 GTPase in canonical Wnt signaling has recently been demonstrated, showing that it is required for ?-catenin translocation to the nucleus. In this study, we investigated the mechanism of Rac1 stimulation by Wnt. Upregulation of Rac1 activity by Wnt3a temporally correlated with enhanced p120-catenin binding to Rac1 and Vav2. Vav2 and Rac1 association with p120-catenin was modulated by phosphorylation of this protein, which was stimulated upon serine/threonine phosphorylation by CK1 and inhibited by tyrosine phosphorylation by Src or Fyn. Acting on these two post-translational modifications, Wnt3a induced the release of p120-catenin from E-cadherin, enabled the interaction of p120-catenin with Vav2 and Rac1, and facilitated Rac1 activation by Vav2. Given that p120-catenin depletion disrupts gastrulation in Xenopus, we analyzed p120-catenin mutants for their ability to rescue this phenotype. In contrast to the wild-type protein or other controls, p120-catenin point mutants that were deficient in the release from E-cadherin or in Vav2 or Rac1 binding failed to rescue p120-catenin depletion. Collectively, these results indicate that binding of p120-catenin to Vav2 and Rac1 is required for the activation of this GTPase upon Wnt signaling.Journal of cell scienceUpon Wnt stimulation, Rac1 activation requires Rac1 and Vav2 binding to p120-catenin.PMC3561852R01 M52112DK082145T32 HD007325HD07325R01 GM052112F32 DK082145Miller RKCodina MCaelles CDunach MVinyoles MDel Valle-Perez BMcCrea PDValls GGarcia de Herreros AfalseUpon Wnt stimulation, Rac1 activation requires Rac1 and Vav2 binding to p120-catenin.A role for Rac1 GTPase in canonical Wnt signaling has recently been demonstrated, showing that it is required for ?-catenin translocation to the nucleus. In this study, we investigated the mechanism of Rac1 stimulation by Wnt. Upregulation of Rac1 activity by Wnt3a temporally correlated with enhanced p120-catenin binding to Rac1 and Vav2. Vav2 and Rac1 association with p120-catenin was modulated by phosphorylation of this protein, which was stimulated upon serine/threonine phosphorylation by CK1 and inhibited by tyrosine phosphorylation by Src or Fyn. Acting on these two post-translational modifications, Wnt3a induced the release of p120-catenin from E-cadherin, enabled the interaction of p120-catenin with Vav2 and Rac1, and facilitated Rac1 activation by Vav2. Given that p120-catenin depletion disrupts gastrulation in Xenopus, we analyzed p120-catenin mutants for their ability to rescue this phenotype. In contrast to the wild-type protein or other controls, p120-catenin point mutants that were deficient in the release from E-cadherin or in Vav2 or Rac1 binding failed to rescue p120-catenin depletion. Collectively, these results indicate that binding of p120-catenin to Vav2 and Rac1 is required for the activation of this GTPase upon Wnt signaling.2012-01-01T00:00:00Z2012 Nov2020-10-08T07:00:19Z2019-03-27T01:04:11ZS-EPMC35618522294605710.1242/jcs.101030